The synaptic pharmacology of an excitatory pathway in the neostriatum was studied using electrophysiological techniques in the tissue slice. 0.4 mm thick slices were maintained in vitro. Electrical stimulation generated a negative extracellular potential in neighboring tissue which was diminished by low calcium or high magnesium solutions, indicating a synaptic step in its production. Antagonists of excitatory amino acids, but not of acetylcholine or dopamine, also blocked the potential reversibly. The anti-spasticity drug baclofen potently blocked the potential as well. Intracellular recordings confirmed the excitatory nature of the potential. Brain legion studies suggested that the fibers originated in cerebral cortex.